The biophysical events which serve as substrates for memory storage have been well documented in Hermissenda B cells, and include a Ca2+-dependent reduction of outward K+ currents and a resultant Increase in membrane input resistance and light-elicited generator potentials. Nevertheless, comparatively little is known about the synaptic events which culminate in these biophysical modifications. In fact, many of the proposed mechanisms thought to underlie the induction of the biophysical memory trace are based on correlative evidence and in some cases are untested. Given that the disparities between various cellular models of learning are most pronounced with regard to the induction process, these assumptions must be more closely examined. Only through such an examination will those ubiquitous principles which govern memory formation be discerned. In the present series of experiments, behavioral, biophysical, and biochemical indices of memory will be employed during induction of an associative memory trace. Hermissenda will serve in all experiments, and is well suited for such an analysis in that its relatively simple nervous system permits the identification and isolation of single cells involved in memory storage. Although both intracellular Ca2+ and specific neurotransmitters have been proposed to participate in the induction of associative memory in Hermissenda, the mechanism by which these cofactors interact to induce new memories is vague. The experiments described here are intended to address the role of these cofactors and the events that they regulate, via behavioral indices of conditioning in conjunction with acute in vivo and in vitro recording and stimulation of identified neurons in the animal's visual-vestibular network. The role of specific transmitters, in particular, GABA and 5-HT, and their effects on neuronal excitability as a function of the physiological state of the postsynaptic neuron will be examined. Mechanisms that underlie trial-by-trial induction of learning will be explored (e.g.,transmitter release paired with postsynaptic Ca2+ elevation), and will be distinguished from the consolidation that takes place both during and after the learning event. A major portion of the present proposal concerns the role of transmitter-activated GTP-binding proteins, both as mediators of Visual-vestibular interactions in Hermissenda, as well as in their function as dual regulators of postsynaptic second messengers which may contribute to the differential modulation of K+ conductance on the postsynaptic membrane. The identification and characterization of mechanisms which causally contribute to Initial induction and subsequent storage of a simple associative memory, and, which can account for a general form of synaptic plasticity, are likely to contribute to the development of unifying principles in the cellular analysis of memory, and may thus provide insight Into specific interventions and treatments to benefit the acquisition and subsequent retrieval of memories.